The ultimate goal of this project is to find an agent that will cause a reversal of preneoplasia in epithelial tissue. Vitamin A and its analogs are the compounds currently being investigated. In optimizing the effect of vitamin A on the differentiation of preneoplastic epithelial tissue three major areas are being studied. (1) The biochemical mechanism of action of vitamin A in the epithelial cell. (2) The metabolism of vitamin A with special emphasis on determining the final active form of the vitamin. (3) The search for analogs of vitamin A (retinoids) that display biological activity in the reversal of preneoplasia and, at the same the, show low toxicity in the animal.